Vassilis Sboros

Heriot-Watt University, Edinburgh, Scotland, United Kingdom

Are you Vassilis Sboros?

Claim your profile

Publications (72)114.9 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The mechanical response of contrast agent microbubbles subject to a static load was investigated in force-deformation curves. Asymptotic relations are fitted with experimental AFM measurements of polymeric microbubbles available in the literature. The elastic modulus and shell thickness are estimated based on the transition from the classical linear (Reissner) to the nonlinear (Pogorelov) regime. The estimated value of the elastic modulus is in the order of GPa and the shell thickness in the order of nm, in good agreement with independent estimates. Numerical simulations recover the above transition and identify a third regime, dominated by the compressibility of the enclosed gas.
    12/2015; 16. DOI:10.1016/j.piutam.2015.03.015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30–100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P<0.05) and reduced antral follicle numbers after 5 weeks (P<0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P<0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P<0.05) and an increased ovarian resistance index (P<0.05) both of which persisted at 5 weeks (P<0.01; P<0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles.
    PLoS ONE 10/2014; 9(10):e111280. DOI:10.1371/journal.pone.0111280 · 3.53 Impact Factor
  • Vassilis Sboros
    [Show abstract] [Hide abstract]
    ABSTRACT: Robust tools for the quantitation of perfusion are not fully developed using contrast enhanced ultrasound (CEUS). The ovine corpus luteum (CL) is a transient gland in the ovary that is formed to produce the hormone progesterone essential for maintenance of pregnancy. Importantly, it has a dense microvascular network with predictable and well-regulated angiogenic mechanisms. In a number of different experiments it was shown that this property may be used to investigate and refine imaging methodology. Using a Philips iU22 ultrasound scanner (Philips Medical Systems Corp, Seattle, WA) in contrast imaging mode it was shown that a highly controlled experiment may produce high levels of reproducibility in the transit of contrast with standard uncertainty below 10%. Also, compartmental kinetics models were tested. The use of prostaglandin F2alpha promotes an intense anti-angiogenesis, allowing monitoring with CEUS prior to and following the demise of the CL microvasculature within 24 hours. Finally, the robust angiogenic property of the CL during the oestrous cycle allows further refinement of CEUS in vivo. In conclusion, the CL offers an attractive changing vascular bed for assessing existing and developing new clinically relevant perfusion imaging methodology.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Microvasculature density (MVD) provides an established biomarker for the prognosis of numerous diseases associated with abnormal microvascular networks. The accurate, robust and timely assessment of MVD changes facilitates disease detection, treatment monitoring and patient stratification. Nevertheless, the current gold standard (PET) for MVD quantification is not used in clinical practice due to its high costs and potential health hazards. Contrast Enhanced Ultrasound (CEUS) imaging can provide an attractive alternative. However, the limited dissociation between larger vessels and microvasculature in the imaged tissues limits the accuracy and robustness of CEUS. This study proposed a novel, and fully automatic technique that dissociates larger vessels from microvasculature in CEUS imaged tissues. The ovine Corpus Luteum (CL) was used as an in vivo model for the development and assessment of the proposed technique.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ultrasound contrast agents are gas filled microbubbles which produced enhanced echoes in ultrasound imaging thus allowing the acquisition of detailed information on the path of blood. It is theoretically known that the size of a vessel affects the behavior of a microbubble, which could potentially be used to discriminate different sized vessels. This information would be useful in the monitoring of neovascularization in tumor growth or treatment. However, currently it is not possible to identify the vessel diameter by any means of signal processing of microbubble echoes. In order to assess microbubble behavior when confined in tubes we compared the acoustic backscatter from biSphere™ microbubbles both free in water and flowing in 200 μm diameter tubes that are similar in size to arterioles. Experimental systems that allow the interrogation of individual microbubbles were designed and modified to allow investigation of both free microbubbles and those in tubes. Unprocessed single microbubble RF data were collected, allowing the calculation of both the fundamental and second harmonic components of the backscattered signal. Microbubbles confined in tubes had lower amplitude response compared to unconfined microbubbles. On consecutive insonations of the same microbubble, free microbubbles produced echoes above noise more often than confined microbubbles. This setup may be used to investigate microbubble behavior in a range of smaller tubes with diameters similar to capillaries thus enabling signal processing design for vessel differentiation.
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper compares the performance between temporal and subband Minimum Variance (MV) beamformers for medical ultrasound imaging. Both adaptive methods provide an optimized set of apodization weights but are implemented in the time and frequency domains respectively. Their performance is evaluated with simulated synthetic aperture data obtained from Field II and is quantified by the Full-Width-Half-Maximum (FWHM), the Peak-Side-Lobe level (PSL) and the contrast level. From a point phantom, a full sequence of 128 emissions with one transducer element transmitting and all 128 elements receiving each time, provides a FWHM of 0.03 mm (0.14λ) for both implementations at a depth of 40 mm. This value is more than 20 times lower than the one achieved by conventional beamforming. The corresponding values of PSL are -58 dB and -63 dB for time and frequency domain MV beamformers, while a value no lower than -50 dB can be obtained from either Boxcar or Hanning weights. Interestingly, a single emission with central element #64 as the transmitting aperture provides results comparable to the full sequence. The values of FWHM are 0.04 mm and 0.03 mm and those of PSL are -42 dB and -46 dB for temporal and subband approaches. From a cyst phantom and for 128 emissions, the contrast level is calculated at -54 dB and -63 dB respectively at the same depth, with the initial shape of the cyst being preserved in contrast to conventional beamforming. The difference between the two adaptive beamformers is less significant in the case of a single emission, with the contrast level being estimated at -42 dB for the time domain and -43 dB for the frequency domain implementation. For the estimation of a single MV weight of a low resolution image formed by a single emission, 0.44 * 109 calculations per second are required for the temporal approach. The same numbers for the subband approach are 0.62 * 109 for the point and 1.33 * 109 for the cyst phantom. The comparison demonstrates similar resolution but slightly lower side-lobes and higher contrast for the subband approach at the expense of increased computation time.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2014; DOI:10.1117/12.2043602 · 0.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The acoustic properties of two clinical (Definity, Lantheus Medical Imaging, North Billerica, MA, USA; SonoVue, Bracco S.P.A., Milan, Italy) and one pre-clinical (MicroMarker, untargeted, Bracco, Geneva, Switzerland; VisualSonics, Toronto, ON, Canada) ultrasound contrast agent were characterized using a broadband substitution technique over the ultrasound frequency range 12-43 MHz at 20 ± 1°C. At the same number concentration, the acoustic attenuation and contrast-to-tissue ratio of the three native ultrasound contrast agents are comparable at frequencies below 30 MHz, though their size distributions and encapsulated gases and shells differ. At frequencies above 30 MHz, native MicroMarker has higher attenuation values and contrast-to-tissue ratios than native Definity and SonoVue. Decantation was found to be an effective method to alter the size distribution and concentration of native clinical microbubble populations, enabling further contrast enhancement for specific pre-clinical applications.
    Ultrasound in medicine & biology 12/2013; 40(3). DOI:10.1016/j.ultrasmedbio.2013.10.010 · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sub-capillary sized microbubbles offer improved techniques for diagnosis and therapy of vascular related disease using ultrasound. Their physical interaction with ultrasound remains an active research field that aims to optimize techniques. The aim of this study is to investigate whether controlled microbubble disruption upon exposure to consecutive ultrasound exposures can be achieved. Single lipid-shelled microbubble scattered echoes have been measured in response to two consecutive imaging pulses, using a calibrated micro-acoustic system. The nonlinear evolution of microbubble echoes provides an exact signature above and below primary and secondary resonance, which has been identified using theoretical results based on the Mooney-Rivlin strain softening shell model. Decaying microbubbles follow an irreversible trajectory through the resonance peak, causing the evolution of specific microbubble spectral signatures. The characteristics of the microbubble motion causes varying amounts of shell material to be lost during microbubble decay. Incident ultrasound field parameters can thus accurately manipulate the regulated shedding of shell material, which has applications for both imaging applications and localized drug delivery strategies.
    Physics in Medicine and Biology 01/2013; 58(3):589-599. DOI:10.1088/0031-9155/58/3/589 · 2.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In diagnostic medicine, microbubbles are used as contrast agents to image blood flow and perfusion in large and small vessels. The small vessels (the capillaries) have diameters from a few hundred micrometers down to less than 10 μ m. The effect of such microvessels surrounding the oscillating microbubbles is currently unknown, and is important for increased sensitivity in contrast diagnostics and manipulation of microbubbles for localized drug release. Here, oscillations of microbubbles in tubes with inner diameters of 25 μm and 160 ¿m are investigated using an ultra-high-speed camera at frame rates of ~12 million frames/s. A reduction of up to 50% in the amplitude of oscillation was observed for microbubbles in the smaller 25-μm tube, compared with those in a 160-μm tube. In the 25-μm tube, at 50 kPa, a 48% increase of microbubbles that did not oscillate above the noise level of the system was observed, indicating increased oscillation damping. No difference was observed between the resonance frequency curves calculated for microbubbles in 25-μm and 160-μm tubes. Although previous investigators have shown the effect of microvessels on microbubble oscillation at high ultrasound pressures, the present study provides the first optical images of low-amplitude microbubble oscillations in small tubes.
    IEEE transactions on ultrasonics, ferroelectrics, and frequency control 01/2013; 60(1):105-14. DOI:10.1109/TUFFC.2013.2542 · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Controlled microbubble stability upon exposure to consecutive ultrasound exposures is important for increased sensitivity in contrast enhanced ultrasound diagnostics and manipulation for localised drug release. An ultra high-speed camera operating at 13 × 106 frames per second is used to show that a physical instability in the encapsulating lipid shell can be promoted by ultrasound, causing loss of shell material that depends on the characteristics of the microbubble motion. This leads to well characterized disruption, and microbubbles follow an irreversible trajectory through the resonance peak, causing the evolution of specific microbubble spectral signatures.
    Applied Physics Letters 08/2012; 101(7). DOI:10.1063/1.4746258 · 3.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study characterized the acoustic properties of an International Electromechanical Commission (IEC) agar-based tissue mimicking material (TMM) at ultrasound frequencies in the range 10-47 MHz. A broadband reflection substitution technique was employed using two independent systems at 21°C ± 1°C. Using a commercially available preclinical ultrasound scanner and a scanning acoustic macroscope, the measured speeds of sound were 1547.4 ± 1.4 m∙s(-1) and 1548.0 ± 6.1 m∙s(-1), respectively, and were approximately constant over the frequency range. The measured attenuation (dB∙cm(-1)) was found to vary with frequency f (MHz) as 0.40f + 0.0076f(2). Using this polynomial equation and extrapolating to lower frequencies give values comparable to those published at lower frequencies and can estimate the attenuation of this TMM in the frequency range up to 47 MHz. This characterisation enhances understanding in the use of this TMM as a tissue equivalent material for high frequency ultrasound applications.
    Ultrasound in medicine & biology 04/2012; 38(7):1262-70. DOI:10.1016/j.ultrasmedbio.2012.02.030 · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study uses atomic force microscopy (AFM) force-deformation (F-Δ) curves to investigate for the first time the Young's modulus of a phospholipid microbubble (MB) ultrasound contrast agent. The stiffness of the MBs was calculated from the gradient of the F-Δ curves, and the Young's modulus of the MB shell was calculated by employing two different mechanical models based on the Reissner and elastic membrane theories. We found that the relatively soft phospholipid-based MBs behave inherently differently to stiffer, polymer-based MBs [Glynos, E.; Koutsos, V.; McDicken, W. N.; Moran, C. M.; Pye, S. D.; Ross, J. A.; Sboros, V. Langmuir2009, 25 (13), 7514-7522] and that elastic membrane theory is the most appropriate of the models tested for evaluating the Young's modulus of the phospholipid shell, agreeing with values available for living cell membranes, supported lipid bilayers, and synthetic phospholipid vesicles. Furthermore, we show that AFM F-Δ curves in combination with a suitable mechanical model can assess the shell properties of phospholipid MBs. The "effective" Young's modulus of the whole bubble was also calculated by analysis using Hertz theory. This analysis yielded values which are in agreement with results from studies which used Hertz theory to analyze similar systems such as cells.
    Langmuir 02/2012; 28(13):5753-60. DOI:10.1021/la204801u · 4.46 Impact Factor
  • Chao Sun, Vassilis Sboros, Mairead Butler, C.M. Moran
    [Show abstract] [Hide abstract]
    ABSTRACT: The effect of microbubble size on the acoustic properties of ultrasound contrast agents has been studied over the clinical frequency range (<10MHz), but comparable research at high frequency is limited. As a further development of high frequency ultrasound in preclinical, intravascular and superficial tissue imaging, this study quantified the attenuation and contrast to tissue ratio (CTR) of two commercial lipid UCAs, Definity and SonoVue, at three populations over the frequency range 12 - 31 MHz at 20 +/- 1 degrees C using a broadband substitution technique. The attenuation and CTR of the two contrast agents in the native and large microbubbles (MBs) population were found to decrease with frequency and the magnitude of the values for the two contrast agents was comparable at the same number concentration. Over this frequency range, large MBs contributed more than 5dB to the CTR than from small MBs.
    Ultrasonics Symposium (IUS), 2012 IEEE International; 01/2012
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nonlinear microbubble oscillations can be exploited by signal processing to provide contrast enhancement in ultrasound imaging. High-speed optical investigations have established that microbubbles resonate in-vitro, but resonance has not yet been established in-vivo. Here we aim to establish the acoustic signature of resonance, which will help identify its occurrence in-vivo and further optimize microbubble signal processing. Resonant microbubbles provide a transient acoustic amplitude response, which is a signature unique to resonance. Large numbers of acoustic signals from single lipid-shelled Definity® microbubbles have been measured using a calibrated micro-acoustic system and a unique transient characteristic of resonance has been identified in the onset of scatter. We present theoretical results based on the Mooney-Rivlin strain softening shell model to show that for realistic shell parameters pulse durations longer than those routinely used in clinical imaging pulses are required to reach a steady state microbubble resonance, indicating the majority of contrast enhancement arises from off-primary resonance microbubble scatter. The specificity of this response may generate higher sensitivity signal processing algorithms, and this should be investigated in the future in realistic vessel sizes to address in vivo requirements.
    Ultrasonics Symposium (IUS), 2012 IEEE International; 01/2012
  • [Show abstract] [Hide abstract]
    ABSTRACT: Microbubbles are used to improve ultrasound imaging of the vascular bed. Optical microscopy has shown microbubbles in different size tubes which have different responses to ultrasound. The acoustic scatter associated with such differences has not been previously measured. Echoes from two types of microbubbles, in narrow tubes, were collected at incident ultrasound parameters relevant to diagnostic imaging. Microbubbles were found to have increased second harmonic signatures in 50 μm diameter tubes compared to 200 μm. There was decreased survival of lipid microbubbles in the smaller tube. Understanding scatter mechanisms in narrow tubes is useful for signal processing optimisation for imaging applications.
    Applied Physics Letters 11/2011; 99(19). DOI:10.1063/1.3657519 · 3.52 Impact Factor
  • Ultrasound in medicine & biology 04/2011; · 2.10 Impact Factor
  • Source
    Yan Yan, James R. Hopgood, Vassilis Sboros
    [Show abstract] [Hide abstract]
    ABSTRACT: The understanding and exploitation of acoustic echo signals from nonlinear ultrasound scatterers is an active research area that aims to improve the sensitivity and specificity of diagnostic imaging. Discriminating between acoustic echoes from linear scatterers, such as tissue, and nonlinear scatterers, such as contrast microbubbles, based on their frequency content is also an important topic in ultrasound contrast imaging. In order to achieve these objectives, a fundamental preliminary stage is to extract information about the reflected signals in the frequency domain with high accuracy: this is essentially a feature extraction and estimation problem. In this paper, a parametric Bayesian spectral estimation method is utilised for the analysis of the backscattered echo signals from microbubbles. In contrast to existing nonparametric discrete-Fourier-transform- (DFT-) based spectral estimation techniques used in the ultrasonic literature, this method is able to estimate the number of spectral components as well as their amplitudes and frequencies. The Bayesian spectral analysis technique has improved frequency resolution compared with the DFT for shortmultiple-component signals at low signal-to-noise ratios. The performance of the method is demonstrated with simulated signals, as well as analysing experimentally measured echo signals from nonlinear microbubble scatterers.
    Journal on Advances in Signal Processing 01/2011; 2011. DOI:10.1155/2011/146175 · 0.81 Impact Factor
  • Ultrasound in Medicine & Biology 01/2011; · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: High frequency ultrasound (>;15 MHz) is used in the fields of pre-clinical, intravascular, ophthalmology and superficial tissue imaging. Tissue-equivalent phantoms have previously been developed to enable relevant quality assurance measurements for frequencies lower than 15MHz but to date limited data is available on the acoustic properties of tissue equivalent material at frequencies higher than 15MHz. In this study, the acoustic attenuation of an International Electromechanical Commission (IEC) agar based tissue mimicking material (TMM) was measured over the frequency range of 12 - 47 MHz at 21 °C ± 1 °C using a broadband substitution technique. By applying a polynomial curve fitting function to the measured data the attenuation (dB·cm-1) was found to vary with frequency f(MHz) in the form of 0.39 f + 0.0069 f2. This result is comparable to the published result at lower frequencies.
    Ultrasonics Symposium (IUS), 2011 IEEE International; 01/2011
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ultrasound contrast agents have been the subject of microvascular imaging research. The sheep corpus luteum (CL) is a microvascular tissue that provides a natural angiogenic and antiangiogenic process, which changes during the luteal phase of the estrous cycle of the ewe. It can also be controlled and monitored endocrinologically, providing a very attractive in vivo model for the study and development of microvascular measurement. The perfusion of the fully developed CL between days 8 and 12 of the estrous cycle was studied in six ewes. A Philips iU22 ultrasound scanner (Bothell, WA, USA) with the linear array probe L9-3 was used to capture contrast-enhanced images after an intravenous bolus injection of 2.4 mL SonoVue (Bracco S.P.A., Milan, Italy). Time-intensity curves of a region of interest inside the CL were formed from linearized image data. A lagged-normal model to simulate the compartmental kinetics of the microvascular flow was used to fit the data, and the wash-in time was measured. Good contrast enhancement was observed in the CLs of all animals and the wash-in time averaged at 5.5 s with 9% uncertainty. The regression coefficient was highly significant for all fits. These data correlated with stained endothelial area in the histology performed postmortem. Two ewes were injected with prostaglandin F2alpha to induce CL regression, which resulted in an increase of wash-in time after a few hours. The CL of the ewe is thus proposed as an ideal model for the study and development of microvascular measurements using contrast ultrasound. Our initial results demonstrate a highly reproducible model for the study of the microvascular hemodynamics in a range of tissues and organs.
    Ultrasound in medicine & biology 01/2011; 37(1):59-68. DOI:10.1016/j.ultrasmedbio.2010.10.013 · 2.10 Impact Factor

Publication Stats

722 Citations
114.90 Total Impact Points

Institutions

  • 2012–2015
    • Heriot-Watt University
      • • School of Engineering and Physical Sciences
      • • Institute of Biological Chemistry, Biophysics and Bioengineering
      Edinburgh, Scotland, United Kingdom
  • 1998–2013
    • The University of Edinburgh
      • • Department of Medical Physics and Medical Engineering
      • • Centre for Cardiovascular Science
      • • Institute for Digital Communications (IDCoM)
      • • School of Clinical Sciences and Community Health
      Edinburgh, Scotland, United Kingdom